The Omicron Is Evolving Rapidly

More SARS-CoV-2 variants are emerging not only in the Delta variant family and even in newer lineages but also in the Omicron variant.

It is completely wrong to say that there is only four Omicron variants that have emerged to date ie the BA.1, BA.1.1, BA.2 and BA.3 as in reality another 3 more major and concerning Omicron sub-lineages have emerged and also many more sub-lineages that have emerged but not yet predominant in circulation.

Most of these new emerging Omicron variants are evolving to not only evade natural and vaccine induced immunity but also developing resistance to the drugs being used including the various monoclonal drugs and also the new antiviral pills recently introduced. In fact, prematurely we can say that it is all these therapeutics that is fueling more mutations and variants to arise and more studies are needed to validate this.

Now researchers from Columbia University Vagelos College of Physicians and Surgeons-New York have in a new study also found that the newer Omicron variants such as the BA.1.1 ie BA.1 with an R346K mutation (BA.1+R346K) and B.1.1.529.2 (BA.2) containing 8 unique spike mutations while lacking 13 spike mutations found in BA.1, have all evolved to evade immunity induced by various therapeutic drugs.
 
The identification of the Omicron variant (B.1.1.529.1 or BA.1) of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) in Botswana in November 20211 immediately raised alarms due to the sheer number of mutations in the spike glycoprotein that could lead to striking antibody evasion.
 
The study team and also other researchers had already previously published study findings confirming such a concern.

https://pubmed.ncbi.nlm.nih.gov/35016198/
https://pubmed.ncbi.nlm.nih.gov/35016195/
https://pubmed.ncbi.nlm.nih.gov/35016194/
https://pubmed.ncbi.nlm.nih.gov/35016196/
https://pubmed.ncbi.nlm.nih.gov/35016199/
Further surveillance of Omicron evolution has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K mutation and BA.2.
The study team therefore extended their studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.1.
 
These three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines.
 
Importantly, BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab), which had retained appreciable activity against BA.1 and BA.1+R346K2.
 
Unfortunately no presently approved or authorized monoclonal antibody therapy could adequately cover all sub-lineages of the Omicron variant and perhaps the use of these drugs are driving the mutations.
 
The study findings were published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2022.02.07.479306v1

For clinically approved or authorized antibodies, only S309 (sotrovimab) retained activity against both BA.1 and BA.1+R346K, but its activity against BA.2 has dropped 27-fold to a 50% inhibitory concentration (IC₅₀) of ∼1 μg/mL .

Only COV2-2130 (cilgavimab) and its combination with COV2-2196 (tixagevimab) retained activity against BA.2, but this antibody combination is only authorized for preventive use. Presently, no authorized therapeutic monoclonal antibody could adequately treat all sublineages of the Omicron variant.

This finding poses a therapeutic dilemma in geographic regions where all three sublineages are present in sufficient numbers. As COVID-19 treatment options are narrowed by the emergence of more and more variants, it is imperative that we continue to devise novel strategies to contain this ever-evolving pathogen.